Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study

Inhibition and substrate requirements of human apical sodium-dependent bile acid transporter (ASBT) and its potential as a prodrug target

The human apical sodium-dependent bile acid transporter (ASBT; SLC10A2) is an important mechanism for intestinal bile acid reabsorption and plays a critical role in bile acid and cholesterol homeostasis. Its physiological role impacts human health and disease. Furthermore, it is a potential candidate for prodrug targeting due to its high transporter capacity and efficiency. However, the understanding of ASBT’s structural determinate of binding and translocation is limited. The work in this dissertation was carried out to study the inhibition and substrate requirement of ASBT, and subsequently to optimize the inhibition assay condition. In particular, work aimed to (1) identify FDA-approved drugs that inhibit ASBT and to derive computational models for ASBT inhibition; (2) evaluate the structural requirements of ASBT by 3D-QSAR analysis using aminopyridine and aminophenol conjugates of chenodeoxycholic acid; (3) synthesis and evaluate in vitro the potential of prolonged release prodrugs via targeting ASBT; (4) identify inhibitor concentrations to efficiently screen and measure inhibition constant K i values against solute carrier transporters; (5) assess compound cytotoxicity on in vitro apparent transporter inhibition. Many FDA-approved drugs from diverse classes, such as the dihydropyridine calcium channel blockers and HMG CoA-reductase inhibitors were found to be ASBT inhibitors. A 3D-QSAR and a Bayesian model were developed using 38 molecules. 3D-QSAR models also were developed using C-24 conjugates. The models concluded that steric and hydrophobic features strongly influenced conjugate interaction with ASBT, and that the relative location of the pyridine nitrogen and substituent groups also modulated binding. Similar values for K i and Kt indicated that substrate binding to ASBT was the rate-limiting step. In vitro results showed that the bile acid conjugates are potential prolonged release prodrugs with binding affinity for ASBT. Experimental conditions for K i screening are suggested to use 10-fold the substrate affinity Kt for potent inhibitors and 100-fold K t for nonpotent inhibitors; for Ki measurement, the inhibitor concentration range should use 0 to estimated K i via five different inhibitor concentrations, where a low range of inhibitor concentrations can be used. For some drugs, their cytotoxicites contributed to or were associated with apparent transporter inhibition, where cytotoxicity differed between MDCK and HEK cells; cytotoxicity is suggested for future studies. Overall, the work carried out in this dissertation will aid in advancement in future prodrug design that exploits ASBT and made recommendations for the efficiency and quality of transporter inhibition assays in general

Evaluation of the re-bond strength of debonded metal and ceramic brackets following Er: YAG laser treatment

Abstract Background Failure of orthodontic bracket bonds is a common occurrence during orthodontic treatment. This study investigated the impact of Er: YAG laser-based removal of adhesive from the bases of metal and ceramic brackets for re-bonding. Methods A total of 168 extracted premolars were collected from patients. 84 metal brackets were used to be bonded on the buccal surface of the premolars in Groups 1, 2, 3 and 4, while 84 ceramic brackets were applied in Groups I, II, III and IV. Group 1/I represented the initial bonding group, with Group 2/II being the re-bonding group with new brackets, while Groups 3/III and 4/ IV received recycled brackets treated by Er: YAG laser or flaming respectively. Both the first and second de-bonding were performed in all samples using a universal testing machine to determine the shear bond strength (SBS). The adhesive remnant index (ARI) was evaluated using a stereo-microscope. The new and the treated bracket bases were evaluated using scanning electron microscopy (SEM). Differences in initial bonding and re-bonding ability were analyzed through one-way ANOVAs, and differences in ARI were assessed with the Kruskal–Wallis test. Results Greater amounts of adhesive residue were observed on ceramic brackets treated by laser. The SBS values for recycled metal brackets in Group 3 (26.13 MPa) were comparable to Group 1 (23.62 MPa) whereas they differed significantly from Group 4 (12.54 MPa). No significant differences in these values were observed when comparing the 4 groups with ceramic brackets. ARI score in Group 4 (2–3 points) differed significantly from the three other groups (P  0.05). SEM analysis didn’t show apparent damage of bracket bases consisting of either metal or ceramic material treated by Er: YAG laser. Conclusions Er: YAG laser treatment was superior to flame treatment as a means of removing adhesive without damaging the brackets. SBS values and ARI scores following Er: YAG laser treatment were similar to those for new brackets, offering further support for Er: YAG laser treatment as a viable means of recycling debonded brackets

Cathode materials of metal-ion batteries for low-temperature applications

Energy storage devices have been developed greatly in recent years. Developing forward, they are expected to operate stably in electric vehicles, electric grids, military equipment, and aerospaces in various climates. Unfortunately, these areas require batteries to be repeatedly and periodically exposed to sub-zero temperatures, even extremely low temperatures (-40 degrees C or lower). The low temperature reduces the kinetics of all the activation processes of the batteries, leading to increased impedance and polarization, and loss of battery energy and power, thus restricting their performance. Developing new cathode materials is one of the main strategies to alleviate the low-temperature restrictions. A conventional lithium-ion battery is the most attractive system, which is more adaptive to the practical low-temperature application now. Sodium ion batteries, magnesium-ion batteries, and zinc-ion batteries, which have the advantages of low cost and high safety, are considered potential substitutes for lithium-ion batteries, the electrochemical performance of these batteries at low-temperature has been conducted extensively. This review provides an overview of lithium-ion batteries, sodium-ion batteries, magnesium-ion batteries, and zinc-ion batteries that can work normally in low-temperature environments, with emphasis on various high-energy cathode materials, mainly including polyanionic compounds, layered oxides, spinel oxides, Prussian blue, and Prussian blue analogs. Specifically, we propose how the conventional low-temperature charge-transfer resistance can be overcome. However, these chemistries also present their own unique challenges at low temperatures. This article discusses the advantages and disadvantages of these materials, as well as the main challenges and strategies for applying them to batteries at low temperatures so that the batteries can still discharge efficiently.(c) 2022 Elsevier B.V. All rights reserved

Cathode materials of metal-ion batteries for low-temperature applications

Energy storage devices have been developed greatly in recent years. Developing forward, they are expected to operate stably in electric vehicles, electric grids, military equipment, and aerospaces in various climates. Unfortunately, these areas require batteries to be repeatedly and periodically exposed to sub-zero temperatures, even extremely low temperatures (-40 degrees C or lower). The low temperature reduces the kinetics of all the activation processes of the batteries, leading to increased impedance and polarization, and loss of battery energy and power, thus restricting their performance. Developing new cathode materials is one of the main strategies to alleviate the low-temperature restrictions. A conventional lithium-ion battery is the most attractive system, which is more adaptive to the practical low-temperature application now. Sodium ion batteries, magnesium-ion batteries, and zinc-ion batteries, which have the advantages of low cost and high safety, are considered potential substitutes for lithium-ion batteries, the electrochemical performance of these batteries at low-temperature has been conducted extensively. This review provides an overview of lithium-ion batteries, sodium-ion batteries, magnesium-ion batteries, and zinc-ion batteries that can work normally in low-temperature environments, with emphasis on various high-energy cathode materials, mainly including polyanionic compounds, layered oxides, spinel oxides, Prussian blue, and Prussian blue analogs. Specifically, we propose how the conventional low-temperature charge-transfer resistance can be overcome. However, these chemistries also present their own unique challenges at low temperatures. This article discusses the advantages and disadvantages of these materials, as well as the main challenges and strategies for applying them to batteries at low temperatures so that the batteries can still discharge efficiently.(c) 2022 Elsevier B.V. All rights reserved

Ramifications of leaders' unethical pro-organizational behavior on employees:Dual-stage moderation of ethical mindset

Although leaders' unethical pro-organizational behavior (UPB) have been identified as one of the key drivers of employees' unethical actions in organizations, our understanding of when and why leader UPB unfolds these adverse effects is still at an early stage. By integrating social cognitive theory with the literature on ethical mindset, the present research sheds light on the cognitive processes and boundary conditions that underpin the effects of leader UPB on followers. We argue that leader UPB may undermine followers' moral efficacy, which in turn translates into heightened follower UPB and general unethical behaviors (UBs). More importantly, we propose that ethical mindset moderates the two stages of the processes, such that followers' outcome-based ethical mindset weakens the effects of leader UPB on follower moral efficacy but strengthens the link between follower moral efficacy and their UPB and UB. The results of two field studies and one experiment provide consistent support for the hypothesized model. Theoretical and practical implications as well as avenues for future research are discussed

Medium-Entropy-Alloy FeCoNi Enables Lithium-Sulfur Batteries with Superb Low-Temperature Performance

Lithium-sulfur battery suffers from sluggish kinetics at low temperatures, resulting in serious polarization and reduced capacity. Here, this work introduces medium-entropy-alloy FeCoNi as catalysts and carbon nanofibers (CNFs) as hosts. FeCoNi nanoparticles are in suit synthesized in cotton-derived CNFs. FeCoNi with atomic-level mixing of each element can effectively modulate lithium polysulfides (LiPSs), multiple components making them promising to catalyze more LiPSs species. The higher configurational entropy endows FeCoNi@CNFs with extraordinary electrochemical activity, corrosion resistance, and mechanical properties. The fractal structure of CNFs provides a large specific surface area, leaving room for volume expansion and Li2S accumulation, facilitating electrolyte wetting. The unique 3D conductive network structure can suppress the shuttle effect by physicochemical adsorption of LiPSs. This work systematically evaluates the performance of the obtained Li2S6/FeCoNi@CNFs electrode. The initial discharge capacity of Li2S6/FeCoNi@CNFs reaches 1670.8 mAh g(-1) at 0.1 C under -20 degrees C. After 100 cycles at 0.2 C, the capacity decreases from 1462.3 to 1250.1 mAh g(-1). Notably, even under -40 degrees C at 0.1 C, the initial discharge capacity of Li2S6/FeCoNi@CNFs still reaches 1202.8 mAh g(-1). After 100 cycles at 0.2 C, the capacity retention rate is 50%. This work has important implications for the development of low-temperature Li-S batteries

Design for a Four-Stage DC/DC High-Voltage Converter with High Precision and a Small Ripple

This paper presents a four-stage DC/DC converter with high precision and a small ripple utilized in an electronic power conditioner (EPC). The galvanically isolated four-stage topology contains four cascade connections: a buck circuit, a push–pull circuit, a power converter, and a voltage regulator. The push–pull switches, as well as the diodes in the output-side rectifier, operate in zero-voltage switching (ZVS) and zero-current switching (ZCS) modes at both switch off and switch on, which helps increase the efficiency. The maximum efficiency of the converter can reach 94.5%. The buck circuit and voltage regulator operate in a two-stage closed-loop condition and, thus, the precision is greater than 0.02%. Due to the voltage regulator, the ripple is less than 1 V when the output voltage reaches 7000 V

Experimental study on direct shear performance of prefabricated splicing joints of ultrahigh-performance concrete

Splicing joints are the weak link of precast ultrahigh-performance concrete (UHPC) segmental bridges (PUSBs). Thus, this paper conducts direct shear tests on eight groups of UHPC keyed joints to investigate the shear performance of the interface of the key. The effects of lateral compressive stress (σn) and the number of keys on the shear performance are also examined. In addition, the load–displacement curves, failure modes, cracking loads, and ultimate loads of the specimens with different parameters are presented. After that, the direct shear capacity of the joints is theoretically analyzed based on the test results and relevant specifications, and a formula for calculating the direct shear capacity is derived. The results show that the failure mode of the UHPC keyed joints is primarily brittle failure. Moreover, the failure mode is the direct shear failure along the interface of the key when the lateral compressive stress is low; however, it is the local crushing of concrete in the key when the lateral compressive stress is high. Additionally, the direct shear capacity of the specimens increases linearly with raising the lateral compressive stress. The direct shear capacity of the double-keyed joints is 17.4–29.3 % higher than that of the single-keyed joints under the same conditions. The values calculated by specifications NF P-18 710 and Eurocode 2 2011 are lower than the experimental ones. The experimental data are evenly distributed on both sides of the curve calculated by specification JSCE 2008 when the lateral compressive stress is low, posing potential hazards in this case. The value predicted by specification AASHTO 2003 is also higher than the experimental value. Finally, we derive a formula for calculating the direct shear performance of the UHPC keyed joints utilizing Mohr’s stress circle theory, and it can be applied to engineering design with high accuracy

Medium-Entropy-Alloy FeCoNi Enables Lithium-Sulfur Batteries with Superb Low-Temperature Performance

Lithium-sulfur battery suffers from sluggish kinetics at low temperatures, resulting in serious polarization and reduced capacity. Here, this work introduces medium-entropy-alloy FeCoNi as catalysts and carbon nanofibers (CNFs) as hosts. FeCoNi nanoparticles are in suit synthesized in cotton-derived CNFs. FeCoNi with atomic-level mixing of each element can effectively modulate lithium polysulfides (LiPSs), multiple components making them promising to catalyze more LiPSs species. The higher configurational entropy endows FeCoNi@CNFs with extraordinary electrochemical activity, corrosion resistance, and mechanical properties. The fractal structure of CNFs provides a large specific surface area, leaving room for volume expansion and Li2S accumulation, facilitating electrolyte wetting. The unique 3D conductive network structure can suppress the shuttle effect by physicochemical adsorption of LiPSs. This work systematically evaluates the performance of the obtained Li2S6/FeCoNi@CNFs electrode. The initial discharge capacity of Li2S6/FeCoNi@CNFs reaches 1670.8 mAh g(-1) at 0.1 C under -20 degrees C. After 100 cycles at 0.2 C, the capacity decreases from 1462.3 to 1250.1 mAh g(-1). Notably, even under -40 degrees C at 0.1 C, the initial discharge capacity of Li2S6/FeCoNi@CNFs still reaches 1202.8 mAh g(-1). After 100 cycles at 0.2 C, the capacity retention rate is 50%. This work has important implications for the development of low-temperature Li-S batteries